1. Field of the Invention
The present invention provides a monoclonal antibody having specificity in neutralizing hIL-20W-induced calf pulmonary artery endothelial cells. The antibody may be used to treat IL-20 inflammation, including artheriosclerosis and rheumatoid arthritis.
2. Description of the Related Art
Inflammatory response is a key component of host defense, but excessive inflammation, such as occurs in arthritis or septic shock, can be harmful or even fatal. Interleukin (IL)-10 was originally described as a cytokine synthesis inhibitory factor because of its inhibitory effect on cytokine production. Because IL-10 suppresses the release and function of a number of proinflammatory cytokines such as IL-1, tumor necrosis factor (TNF)-α, and IL-6, it is a normal endogenous feedback factor for the control of immune responses and inflammation. Autoimmune models of rheumatoid arthritis, thyroiditis, and collagen-induced arthritis, as well as a model of herpetic stromal keratitis, suggest the negative regulatory roles of IL-10 on inflammation and immunopathology. However, IL-10 is also a stimulatory factor for mast cells, B cells, and thymocytes; it is pleiotropic and acts on many other cell types, including monocytes macrophages, T cells, natural killer (NK) cells, neutrophils, endothelial cells, and peripheral blood mononuclear cells (PBMCs). IL-10 can inhibit the generation of new vessels within tumors both directly by acting on the tumor cells and indirectly by influencing infiltrating immune cells. Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by the progressive accumulation of lipids, extracellular matrix, and cells, including macrophages, T lymphocytes, and smooth muscle cells. Inflammation plays a major role in atherosclerosis plaque disruption and thrombosis, and therefore greatly influences the occurrence of coronary syndromes and mortality. IL-10, important in atherosclerosis lesion formation and stability, is a protective factor against the effect of environmental pathogens on atherosclerosis.
Several new members of the IL-10 family, including IL-19, IL-20, IL-22, MDA-7 (IL-24), and AK155 (IL-26), have only recently been discovered. IL-19 was first discovered in LPS-treated monocytes. IL-19 induces the production of IL-6 and TNF-α from monocytes and of Th2 cytokines from CD4+ T cells, and is associated with asthma.
IL-20 is preferentially expressed in monocytes. Overexpression of IL-20 in transgenic mice causes neonatal death as well as skin abnormalities, including aberrant epidermal differentiation. IL-20 selectively enhances multipotential hematopoietic progenitors in vitro and in vivo. IL-20 induces STAT 3 activation through binding to two types of IL-20 receptor (R) complexes, either IL-20RI and IL-20R2 or IL-20R2 and IL-22R. Stimulation of HepG2 human hepatoma cells with IL-22 upregulates the production of acute phase reactants like serum arnyloid A, α1-antichymotrypsin, and haptoglobin. IL-22 plays a protective role in T-cell-mediated murine hepatitis and increases the innate immunity of tissues. Expression of IL-24 was upregulated in wound healing and during the in vitro differentiation of a melanoma cell line. IL-26 is induced by the transformation of T lymphocytes with Herpesvirus Saimiri, and targets epithelial cells through IL-20R1 and IL-10R2.
Little is known about the in vitro biologic function of IL-20, except that it induces the proliferation of keratinocytes. Our aims, therefore, were to explore whether IL-20 acts on target cells other than keratinocytes. We also wanted to analyze whether IL-20, like IL-10, has any association with inflammatory diseases such as atherosclerosis and rheumatoid arthritis; thus, we treated calf pulmonary artery endothelial cells (CPAEs) with human (h)IL-20 and monitored the proliferation of the cells. We also treated the endothelial cells with both IL-10 and IL-20 and demonstrated that IL-10 antagonized the activity of IL-20. ApoE-deficient (ApoE−/−) mice reveal the phenotype of atherosclerosis. Therefore, we performed immunohistochemical staining on the aortic arch of ApoE−/− mice and demonstrated that IL-20 was expressed on atherosclerotic plaque and that its receptors, IL-20RI and IL-20R2, were upregulated on the endothelium and atherosclerotic plaque.